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CT perfusion imaging of lung cancer: benefit of motion correction for blood flow estimates.

PURPOSE: CT perfusion (CTP) imaging assessment of treatment response in advanced lung cancer can be compromised by respiratory motion. Our purpose was to determine whether an original motion correction method could improve the reproducibility of such measurements. MATERIALS AND METHODS: The institutional review board approved this prospective study. Twenty-one adult patients with non-resectable non-small-cell lung cancer provided written informed consent to undergo CTP imaging. A motion correction method that consisted of manually outlining the tumor margins and then applying a rigid manual landmark registration algorithm followed by the non-rigid diffeomorphic demons algorithm was applied. The non-motion-corrected and motion-corrected images were analyzed with dual blood supply perfusion analysis software. Two observers performed the analysis twice, and the intra- and inter-observer variability of each method was assessed with Bland-Altman statistics. RESULTS: The 95% limits of agreement of intra-observer reproducibility for observer 1 improved from -84.4%, 65.3% before motion correction to -33.8%, 30.3% after motion correction (r = 0.86 and 0.97, before and after motion correction, p < 0.0001 for both) and for observer 2 from -151%, 96% to -49 %, 36 % (r = 0.87 and 0.95, p < 0.0001 for both). The 95% limits of agreement of inter-observer reproducibility improved from -168%, 154% to -17%, 25%. CONCLUSION: The use of a motion correction method significantly improves the reproducibility of CTP estimates of tumor blood flow in lung cancer. KEY POINTS: • Tumor blood flow estimates in advanced lung cancer show significant variability. • Motion correction improves the reproducibility of CT blood flow estimates in advanced lung cancer. • Reproducibility of blood flow measurements is critical to characterize lung tumor biology and the success of treatment in lung cancer.

Assessing response to treatment in non--small-cell lung cancer: role of tumor volume evaluated by computed tomography.

INTRODUCTION: We set out to investigate whether volumetric tumor measurements allow for a prediction of treatment response, as measured by patient survival, in patients with advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Patients with nonresectable NSCLC (stage III or IV, n = 100) who were repeatedly evaluated for treatment response by computed tomography (CT) were included in a Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study. Tumor response was measured by comparing tumor volumes over time. Patient survival was compared with Response Evaluation Criteria in Solid Tumors (RECIST) using Kaplan-Meier survival statistics and Cox regression analysis. RESULTS: The median overall patient survival was 553 days (standard error, 146 days); for patients with stage III NSCLC, it was 822 days, and for patients with stage IV disease, 479 days. The survival differences were not statistically significant (P = .09). According to RECIST, 5 patients demonstrated complete response, 39 partial response, 44 stable disease, and 12 progressive disease. Patient survival was not significantly associated with RECIST class, the change of the sum of tumor diameters (P = .98), nor the change of the sum of volumetric tumor dimensions (P = .17). CONCLUSION: In a group of 100 patients with advanced-stage NSCLC, neither volumetric CT measurements of changes in tumor size nor RECIST class significantly predicted patient survival. This observation suggests that size response may not be a sufficiently precise surrogate marker of success to steer treatment decisions in individual patients.

The role of aortic wall CT attenuation measurements for the diagnosis of acute aortic syndromes.

OBJECTIVES: To determine if measurements of aortic wall attenuation can improve the CT diagnosis of acute aortic syndromes. METHODS: CT reports from a ten year period were searched for acute aortic syndromes (AAS). Studies with both an unenhanced and a contrast enhanced (CTA) series that had resulted in the diagnosis of intramural hematoma (IMH) were reviewed. Diagnoses were confirmed by medical records. The attenuation of aortic wall abnormalities was measured. The observed attenuation threshold was validated using studies from 39 new subjects with a variety of aortic conditions. RESULTS: The term "aortic dissection" was identified in 1206, and IMH in 124 patients' reports. IMH was confirmed in 31 patients, 21 of whom had both unenhanced and contrast enhanced images. All 21 had pathologic CTA findings, and no CTA with IMH was normal. Attenuation of the aortic wall was greater than 45 HUs on the CTA images in all patients with IMH. When this threshold was applied to the new group, sensitivity for diagnosing AAS was 100% (19/19), and specificity 94% (16/17). Addition of unenhanced images did not improve accuracy. CONCLUSIONS: Measurements of aortic wall attenuation in CTA have a high negative predictive value for the diagnosis of acute aortic syndromes.

Causes of death of patients with lung cancer.

CONTEXT: The causes of death for patients with lung cancer are inadequately described. OBJECTIVE: To categorize the immediate and contributing causes of death for patients with lung cancer. DESIGN: The autopsies from 100 patients who died of lung cancer between 1990 and February 2011 were analyzed. RESULTS: Tumor burden was judged the immediate cause of death in 30 cases, including 26 cases of extensive metastases and 4 cases with wholly or primarily lung tumor burden (causing respiratory failure). Infection was the immediate cause of death for 20 patients, including 8 with sepsis and 12 with pneumonia. Complications of metastatic disease were the immediate causes of death in 18 cases, including 6 cases of hemopericardium from pericardial metastases, 3 from myocardial metastases, 3 from liver metastases, and 3 from brain metastases. Other immediate causes of death were pulmonary hemorrhage (12 cases), pulmonary embolism (10 cases, 2 tumor emboli), and pulmonary diffuse alveolar damage (7 cases). From a functional (pathophysiologic) perspective, respiratory failure could be regarded as the immediate cause of death (or mechanism of death) in 38 cases, usually because of a combination of lung conditions, including emphysema, airway obstruction, pneumonia, hemorrhage, embolism, resection, and lung injury in addition to the tumor. For 94 of the 100 patients, there were contributing causes of death, with an average of 2.5 contributing causes and up to 6 contributing causes of death. CONCLUSIONS: The numerous and complex ways lung cancer kills patients pose a challenge for efforts to extend and improve their lives.

Flat panel volume computed tomography of the coronary arteries.

RATIONALE AND OBJECTIVES: Multidetector-row computed tomography (MDCT) has evolved into a sensitive diagnostic tool for the noninvasive detection of coronary artery stenosis, but remains limited by spatial resolution. Flat panel volume computed tomography (fpVCT) offers a higher spatial resolution. In a postmortem investigation of autopsy specimens, the accuracies of fpVCT for measuring the severity of coronary artery stenosis and the size of atherosclerotic plaque components were determined. METHODS AND MATERIALS: In 25 autopsy cases, hearts were isolated, the left anterior descending coronary arteries filled with contrast agent, and depicted with a prototype fpVCT unit with a slice thickness of 0.25 mm. Transections of the left anterior descending coronary arteries were reconstructed and compared with histopathologic sections using light microscopy. RESULTS: FpVCT measurements of luminal stenosis (r = 0.81), total plaque area (r = 0.88), calcified plaque area (r = 0.92), noncalcified plaque area (r = 0.83), and lipid core size (r = 0.67; P < .02) correlated well with histopathology (P < .0001). The limits of agreement for measuring any plaque component were three times smaller than those reported for MDCT. CONCLUSIONS: Postmortem coronary fpVCT provides an accurate and reproducible method for the quantitative assessment of both luminal stenosis and atherosclerotic plaque size. Because of its high spatial resolution, the method should be sufficiently accurate to reliably detect the lipid pools of vulnerable plaques.

Progression of coronary atherosclerosis after heart transplantation on electron-beam computed tomography.

RATIONALE AND OBJECTIVES: Cardiac transplant vasculopathy is the most important long-term complication of heart transplantation, with overlapping features with conventional, atherosclerotic coronary artery disease. The aim of this study was to determine the progression of coronary artery disease after heart transplantation by measuring total coronary calcium load. MATERIALS AND METHODS: After heart transplantation, 185 patients were serially examined using electron-beam computed tomography for coronary calcium load for clinical reasons. The mean time between the initial examination and the follow-up scan was 566 days (range, 126-1,436). Coronary calcium load was measured by the Agatston method, and the total calcium scores at both examinations were compared between patients taking and those not taking lipid-lowering medications (statins). RESULTS: Patients not taking statins (n = 94) displayed a median annualized percentage increase in total calcium score of 0 Agatston units, whereas patients taking at least the lowest recommended daily dose of a statin (n = 84) displayed an annualized percentage decrease of 11 Agatston units. The difference was not statistically significant (Wilcoxon's rank-sum test, P = .35). Only 17 patients had increases of > 24 Agatston units, and eight of them were taking statins (chi(2) test, P = .99). CONCLUSION: The annual rate of progression of coronary calcium load after heart transplantation is low. In this investigation, no beneficial effects of statins could be detected.

Characterization of atherosclerotic plaques in human coronary arteries with 16-slice multidetector row computed tomography by analysis of attenuation profiles.

RATIONALE AND OBJECTIVES: We investigated if 16-slice multidetector row computed tomography (MDCT) allows correct classification of coronary plaques into calcified or noncalcified and further subclassification of noncalcified plaques into either lipid-rich with a necrotic core or fibrous. MATERIALS AND METHODS: Coronary arteries of 30 isolated hearts were filled postmortem with a contrast medium and scanned with a 16-slice MDCT imager (Light Speed 16 pro, GEMS, Milwaukee, WI). Imaging parameters: collimation 16 x 0.625 mm, pitch 0.325, tube voltage 120 kV, tube current 250 mA, and gantry rotation time 500 milliseconds. The images were reformatted perpendicular to the axis of the coronary arteries (AW 4.2 software, GEMS) and analyzed by establishing attenuation profiles of the coronary cross sections (ImageJ 1.33n software, NIH, Bethesda, MD). Results were compared with the correlating histopathologic sections of the arteries. RESULTS: Analysis of 195 CT cross-sections showed a sensitivity and specificity for the correct classification of calcified plaques of 100% and 97.3% and for noncalcified plaques of 80.8% and 95.1%, respectively. The attenuation of epicardial fat ranged from -119 Hounsfield units (HU) to 23 HU (median -71 HU), and from 93 HU to 625 HU (308 HU) for the contrast medium. Calcified plaques showed an attenuation between 333 HU and 1944 HU (1,089 HU), noncalcified plaques between 26 HU and 124 HU (52 HU). Further subclassification of noncalcified plaques showed attenuation values between 26 HU and 67 HU (median 44 HU) for lipid-rich plaques with a necrotic core and from 37 HU to 124 HU (median 67 HU) for fibrous plaques. CONCLUSIONS: Coronary atherosclerotic plaques can be reliably identified and classified as either calcified or noncalcified by 16-slice MDCT in postmortem studies. Further differentiation of noncalcified plaques in either lipid-rich or fibrous is not reliably feasible because of substantial overlap of the attenuation.

Dynamic high-resolution electron-beam CT scanning for the diagnosis of bronchiolitis obliterans syndrome after lung transplantation.

PURPOSES: To determine the diagnostic capabilities of dynamic high-resolution electron-beam (HREB) CT scanning for diagnosing bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. MATERIALS AND METHODS: At the time of follow-up examinations after lung transplantation, 52 patients were examined by dynamic HREB CT scan. Visual signs of small airway disease were assessed and compared with lung function. For numerical analysis, the mean lung attenuation and its SD were determined and compared with the course of lung function tests. RESULTS: On visual analysis, significant parenchymal attenuation inhomogeneities were present in eight of nine patients with manifest BOS, and in two of four patients who developed BOS during follow-up. Thirteen of 20 patients with persistent normal lung function displayed homogeneous lung attenuation. On numerical analysis, mean lung attenuation was significantly lower in patients who developed BOS during follow-up than in patients with persistent normal lung function (both in expiration and inspiration, p < 0.0001). With an optimal threshold, the sensitivity was 100% (4 of 4 patients) and the specificity was 90% (19 of 20 patients). In patients with BOS at the time of the CT scan examination, parenchymal attenuation was less homogeneous than in patients with persistent normal lung function (p < 0.0001). With an optimal threshold, the sensitivity was 78% (7 of 9 patients) and the specificity was 85% (17 of 20 patients). CONCLUSIONS: Dynamic HREB CT of lung transplant recipients correlates well with lung function criteria of BOS at the time of the CT examination and with the subsequent progression to BOS.

Assessment of coronary artery stent patency by electron-beam CT.

Following coronary angioplasty and stent implantation, restenosis remains common and its outcome difficult to predict. We set out to determine the diagnostic accuracy of electron-beam computed tomography (EBCT) for the non-invasive detection of stent obstruction. In a prospective, blinded investigation, we included 152 coronary artery segments in 117 patients treated with a stent implant. All segments were evaluated by a dynamic EBCT study that depicted contrast bolus passage distal to the stent and a CT angiographic study of the entire coronary arteries. It was found that delayed contrast enhancement in the distal segment correlated with angiographic stent obstruction (Spearman's rank correlation, P=0.008), while all other indicators of stent occlusion did not correlate with angiographic diagnosis. However, direct comparison of patients with obstruction of less vs. more than 75% of luminal diameter did not yield any statistically significant differences of distal enhancement delay, and for the detection of >90% occlusion, the sensitivity was 72% at a specificity of 60%. Although delayed contrast enhancement distal to the stent upon EBCT did correlate with angiographical obstruction, the correlation did not suffice to appear clinically satisfactory.

Gauging effective spatial resolution in multirow helical cardiac computed tomography with a dynamic phantom.

PURPOSE: To devise a numerical indicator of image quality for multirow helical cardiac computed tomography (CT) and its relation to temporal resolution. MATERIALS AND METHODS: A pulsatile cardiac assist device was used to simulate cardiac wall motion by mechanically transmitting the device dynamics to a piece of tungsten wire. Wire motion induced by different device rates was captured with an 8-row subsecond helical CT scanner operating with various scanning parameters. Image artifacts were visually assessed and compared with the image point spread function (PSF) using the full width at half maximum (FWHM) area as a numerical estimate of spatial accuracy. RESULTS: At rest, the FWHM area was determined as 1.3 mm2. At a device rate of 60 bpm, the FWHM area ranged from 1.51 mm2 to 21.62 mm2, depending on the time of image reconstruction. Mean reproducibility of the FWHM area measurements was determined as 0.05, whereas visual estimates of motion artifact were highly variable between different readers (kappa = 0.19). Visually determined image quality correlated closely with the FWHM area metric (Spearman's rank correlation, P = 0.0001, rho = 0.841). At a device rate of 100 bpm, the minimum FWHM area was 2.00 mm2 using a single-sector algorithm, 1.41 mm2 using a 2-segment algorithm, and 1.37 mm2 using a 4-segment algorithm. CONCLUSIONS: Use of a pulsatile cardiac assist device could serve as an in vitro test bed for cardiac CT imaging methods. Area FWHM of the PSF correlates well with visually determined image quality of a dynamic phantom, but provides better reproducibility than visual analysis.

Coronary artery calcium scoring: diagnostic accuracy of different software implementations.

PURPOSE: To compare the diagnostic power of different software implementations for the quantification of coronary artery calcium. MATERIALS AND METHODS: Electron beam computed tomography was performed in 109 heart transplant recipients at the same time as catheter coronary angiography and intracoronary ultrasound. Electron beam computed tomography images were analyzed by 3 software packages marketed for the quantification of coronary calcifications using the same software settings, and the resultant calcium scores correlated with the invasive reference methods by Bland-Altman plots and analysis of the receiver operating characteristics. RESULTS: Although all scoring systems displayed close correlations upon regression analysis (r2=0.94-0.99), their ability to detect disease as per the invasive reference method varied significantly in some instances. The area under the ROC curve varied between Az=0.78 and 0.85 for the detection of coronary artery stenosis upon coronary angiography (P=0.05-0.13), and between Az=0.75 and 0.83 for the detection of accelerated intimal proliferation (P=0.03-0.18). CONCLUSIONS: Different software implementations for the quantification of coronary artery calcium load may display diagnostically relevant differences in spite of close direct correlation.

Bronchiolitis obliterans syndrome in lung transplant recipients: use of spirometrically gated CT.

PURPOSE: To assess the potential use of spirometrically gated lung computed tomographic (CT) findings in the diagnosis of bronchiolitis obliterans syndrome after lung transplantation. MATERIALS AND METHODS: Forty-nine lung transplant recipients were examined at least 8 months after surgery with spirometrically gated thin-section CT of the lung. In addition to visual signs of small-airway disease at CT, mean lung attenuation and the SD were numerically determined and compared with the results of lung function testing at the time of the CT examination and 1 year later by using factorial analysis of variance. RESULTS: Mean lung attenuation was significantly lower in patients who developed bronchiolitis obliterans syndrome within 1 year after the CT study (-837 HU +/- 3) than in patients with persistent normal lung function (-812 HU +/- 3, P <.001). With an optimal threshold, sensitivity was 69%, specificity was 71%, and accuracy was 84%. Visual analysis did not significantly contribute to the prognostic power of CT. CONCLUSION: Spirometrically gated CT measurements of lung attenuation can be used to predict the onset of bronchiolitis obliterans syndrome after lung transplantation.

Magnetic resonance imaging of inflammatory bowel disease: evaluation in a rabbit model.

PURPOSE: To correlate intestinal contrast enhancement and wall thickening with the degree of inflammation in an experimental model of inflammatory bowel disease. MATERIALS AND METHODS: Inflammatory bowel disease was elicited in 39 New Zealand White rabbits by rectal instillation of 2,4,6-trinitrobenzene sulphonic acid (TNBA). Magnetic resonance imaging (MRI) was used to determine bowel wall thickness and intestinal contrast enhancement after the administration of 0.1 mmol/kg of gadodiamide intravenously. MR measurements were compared with the complete histopathologic analysis. RESULTS: MR measurements of bowel wall thickness correlated well with histopathologic measurements in vitro (r = 0.85, P < 0.0001) and with histopathologic evidence of chronic inflammatory bowel disease (P < 0.02). Chronic inflammation was characterized by increased intestinal contrast enhancement (137 +/- 25%) when compared to normal bowel (86 +/- 7%, P = 0.04). CONCLUSION: Contrast-enhanced MRI accurately reflects inflammatory bowel disease in the rabbit model.